1. Field of the Invention
This invention pertains to pharmaceutical manufacturing and particularly to supplying pharmaceutical dosage forms, such as medicinal tablets or capsules, uniformly oriented at a step in their manufacture. The dosage form rectifier of the present invention receives randomly oriented dosage forms, maintains or rectifies the orientation as appropriate and delivers uniformly oriented dosage forms.
2. Description of the Related Art Including Information Disclosed Under 37 CFR 1.97 and 1.98
Pharmaceutical dosage forms, e.g., tablets, capsules and the like are made and consumed in enormous quantities. Accordingly, specialists in the art of pharmaceutical manufacturing have made great investments in equipment for making, filling, closing, labeling, inspecting and packaging such dosage forms at high volume and with high efficiency. Also, in the interest of efficiency, many devices and methods have been developed for integrating the various processing steps and for transferring the dosage forms from station to station where the various processing steps occur. Certain processing steps including, for example, capsule filling, marking or printing, inspecting and packaging steps, generally require that the dosage forms be uniformly oriented at a particular processing station or location for that processing step. For example, it may be necessary to provide gel capsules oriented caps-up, caps-forward or caps all to one side or to provide tablets oriented edge-forward or lying flat, relative to a conveyor path supplying the dosage forms to a particular processing station. Preferably, the equipment for ensuring uniform orientation should be compact, reliable and efficient and should be readily integrable with other components of the processing system.
Pharmaceutical dosage forms generally are not shaped as perfect spheres or perfect cubes. Instead, dosage forms have physical geometries that can be discriminated to some extent for orientation purposes. For example, many tablets have a flattened or concave, round or oval shape or a flattened or concave, parallelogram shape such that the front and back surfaces are relatively broad and the surrounding edge surfaces are relatively narrow. Capsules or capsule-shaped tablets are also common and these have a larger length aspect and a smaller width or circumference aspect. For many processing steps, the orientation of dosage forms on the basis of the difference in geometric dimensions is sufficient and many mechanical devices for transporting and processing of dosage forms oriented on this basis are known. For example, conveyor paths and processing stations may be configured such that dosage forms may be transported or held only in a specific orientation such as lengthwise or edgewise.
Another type of dosage form, the two-part gel capsule filled with liquid or solid medicament, provides an additional physical aspect that may be exploited for purposes of orienting the dosage forms. Such gel capsules comprise a body and a cap that is somewhat wider than the body and that typically is telescoped onto, or otherwise affixed to, the body to close the capsule. Because the cap is slightly larger in circumference than the body, the cap end can be mechanically distinguished from the body end of the capsule and many devices have been developed for this purpose. These devices provide a variety of cavities, channels, fingers, brushes and the like which cooperate to sort or rotate the dosage forms in an orientation-specific manner, i.e., cap end versus body end. Friction or mechanical interference provides the basis for discriminating between the wider cap end and the narrower body end as, for example, where a path for tumbling or sliding is calibrated such that the body end, but not the cap end, will sink into a depression, or one end but not the other will tumble a certain way or one end is held back by friction.
The above-described devices for orienting dosage forms that rely on external physical dimensional differences are sufficient for processing of many dosage forms. A unique problem arises, however, when pharmaceutical dosage forms must be uniformly oriented for a particular processing step but external physical dimensional differences within the dosage forms are not sufficient to discriminate between proper and improper orientation.
For example, certain dosage forms must be oriented for certain processing steps with respect to an internal, i.e., formulation, non-symmetry wherein the dosage form contains formulation components that differ at different locations within or upon the dosage form. Examples of dosage forms exhibiting such formulation non-symmetry include multi-layered tablets having different ingredients in different layers such as a buffered aspirin product having aspirin in one layer and a buffering agent in another layer. Another example is multi-layer osmotic dosage forms having an internal compartment surrounded by a semipermeable membrane and having a delivery port formed through the semipermeable membrane. The internal compartment contains at least one drug-containing layer and at least one expandable polymer-containing layer. The expandable polymer-containing layer is known as a "push" layer because, following oral administration, fluid is imbibed through the semipermeable membrane causing the drug-containing layer to form a deliverable drug formulation and causing the polymer layer to expand and "push" the drug formulation through the delivery port. Such osmotic dosage forms are typically manufactured by compressing the component drug-containing layer(s) and the push layer(s) together to form a core, applying the semipermeable membrane around the core and then drilling, typically with a laser, an appropriate delivery port. The dosage form is non-symmetrical in that one or more portions contain the drug-containing layer(s) and one or more portions contain the push layer(s). Generally, the dosage form is configured to have a "push end" adjacent to a push layer and a "drug-release end" that is adjacent to a drug-containing layer or that will become adjacent to a drug-containing layer following fluid imbibition into the dosage form. The dosage form may be shaped in a variety of configurations including conventional tablet shapes wherein the layers are compressed transversely such that a broad front surface encompasses the drug-release end and the opposite broad back surface encompasses the push end. Certain dosage forms are preferably capsule-shaped and have the layers compressed longitudinally such that the drug-release end is at one narrow end of the capsule-shaped tablet and the push end is at the opposite narrow end of the capsule-shaped tablet. No matter what the dosage form shape, however, proper operation of the dosage form requires that the delivery port be formed in the drug-release end of the dosage form and not at the push end of the dosage form.
In view of the above, it will be appreciated that orienting the dosage forms merely with respect to physical dimensions is not sufficient for the laser drilling process, i.e., drilling must occur only at one of alternate but dimensionally identical surfaces such as the front or back surface of a conventional tablet-shaped dosage form or one or the other narrow and rounded ends of a capsule-shaped dosage form. Thus, while the dosage forms may be oriented dimensionally so that an appropriate dimensional "end" is presented for drilling, this orientation is random with respect to whether the end presented is actually the correct end for drilling of the delivery port, i.e., the drug-release end and not the push end of the dosage form.
One approach to this problem of orienting dosage forms with respect to an internal formulation non-symmetry uses a system wherein dosage forms are supplied in a manner that permits laser access to alternate surfaces of the dosage form, e.g., a front and a back surface of a conventional tablet-shaped dosage form. A suitable detector is used to determine which of the alternate surfaces is the proper surface for drilling, i.e., the drug-release end, and a laser controller directs the laser to drill the correct surface. Such methods and apparatus are disclosed and claimed in U.S. Pat. Nos. 5,658,474 and 5,698,119, owned by Alza Corporation, each of which is incorporated in its entirety by reference herein.
The above-described approach is especially useful for dosage forms wherein the surface of the dosage form that is desired to be drilled is relatively large and wherein the dosage forms can be securely transported in an attitude that provides laser access to the alternate surfaces. For example, osmotic dosage forms having a conventional tablet shape with relatively broad front and back surfaces and narrow edge surfaces can be positioned on edge and securely transported such that either the front or the back surfaces are accessible to the laser. Upon determining which of the surfaces is adjacent to the drug-containing layer within the core, typically by a color detector for detecting a colorant used in at least one layer within the core, the laser is directed to drill that surface. This approach has been shown to be unsatisfactory, however, for capsule-shaped osmotic dosage forms wherein the delivery port is desired to be drilled into the surface at one of the relatively small and rounded ends of the dosage forms because these dosage forms are difficult to securely transport in an attitude that would permit laser access to either of the small end surfaces.
Another approach to this problem, common to many known orienting devices, is to supply randomly oriented dosage forms but, upon determining whether the orientation is correct for drilling, drilling only the properly oriented dosage forms and rejecting and recycling the improperly oriented dosage forms. Eventually, as the recycled dosage forms are randomly oriented for each drill presentation cycle, the proper orientation for drilling will be obtained and the dosage forms will be drilled. This approach is relatively inefficient, however, as approximately half of the dosage forms presented in each randomly oriented drill presentation cycle will be improperly oriented and will require recycling.
Accordingly, it would be an advance in the art to provide methods and apparatus for receiving randomly oriented dosage forms, maintaining or rectifying the orientation as appropriate and delivering uniformly oriented dosage forms. It would be a particular advance to provide such methods and apparatus that do not rely on physical dimensional differences to rectify orientation and thus may be used to uniformly orient dosage forms when physical dimensional differences are insufficient for proper orientation. Such methods and apparatus would be useful and efficient for providing uniformly oriented dosage forms for various processing steps and would be especially useful for ensuring that pharmaceutical dosage forms having internal formulation non-symmetry are uniformly oriented for laser drilling. Additionally, it would be an advance to provide such methods and apparatus that are compact, reliable and efficient and that may be readily integrated with other components of a pharmaceutical dosage form processing system.